Systems and methods for removal of blood and thrombotic material

ABSTRACT

A system for aspirating thrombus includes a catheter having a supply lumen having a distal end and an aspiration lumen configured to couple to a vacuum source and having an interior wall surface and an open distal end, an orifice at or near the distal end of the supply lumen, in fluid communication with the interior of the aspiration lumen, the orifice located proximally of the open distal end of the aspiration lumen, wherein the orifice is configured to create a spray pattern that impinges on the interior wall surface of the aspiration lumen when a distal end of the aspiration catheter is immersed within an aqueous environment, and a disposable tubing set having a first conduit configured to couple the supply lumen of the aspiration catheter to a fluid source, and a pump component associated with the first conduit and configured to detachably couple to a drive unit.

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/493,584, filed on Apr. 21, 2017, which is a continuation of U.S.patent application Ser. No. 14/715,451, filed on May 18, 2015, whichclaims the benefit of priority to U.S. Provisional Application No.62/000,448, filed on May 19, 2014, all of which are incorporated byreference in their entirety herein for all purposes. Priority is claimedpursuant to 35 U.S.C. § 120 and 35 U.S.C. § 119.

BACKGROUND OF THE INVENTION Field of the Invention

The present disclosure pertains generally to medical devices and methodsof their use. More particularly, the present invention pertains toaspiration and thrombectomy devices and methods of use thereof.

Description of the Related Art

Several devices and systems already exist to aid in the removal ofthrombotic material. These include simple aspiration tube type devicesusing vacuum syringes to extract thrombus into the syringe, simpleflush-and-aspirate devices, more complex devices with rotatingcomponents the pull in, macerate and transport thrombotic material awayfrom the distal tip using a mechanical auger, systems that use very highpressure to macerate the thrombus and create a venturi effect to flushthe macerated material away.

All of the devices described above have limitations as a result ofindividual design characteristics. For example, simple aspirationcatheters offer ease of use and rapid deployment but may become blockedor otherwise inoperable when faced with older, more organized thromboticmaterial. Such devices must be removed and cleared outside the body andthen re-inserted into the vasculature, which lengthens the time neededfor the procedure and increases the opportunity to kink the cathetershaft. Such kinks may reduce performance by decreasing thecross-sectional area of the catheter or may render the deviceinoperable.

Mechanical rotary devices use an auger to grab and carry the thrombusaway from the target area. Some create transport force via vacuumbottles while others create differential pressure at the distal tip ofthe device with the auger acting as a low pressure pump. These devicestypically work slowly and offer the physician no feedback as to when thedevice should be advanced further into the lesion.

Flushing type devices include manual flush type devices in which thephysician manipulates a hand-driven pump to provide flowing saline atthe tip of the device to break up and aspirate the thrombus material,which may introduce performance variations based on the ability of thephysician to consistently pump the device over the duration of theprocedure. Flushing devices also include high pressure flushing devicesthat macerate the thrombus and then, using a vortex created by the highpressure fluid, transport the emulsified thrombotic material to acollection bag. These devices are effective at removing all levels ofthrombotic material, but the pressure created by the device is so greatthat its action against certain vessel walls may interrupt the heartmuscle stimulation mechanism and create a bradycardia event in certainpatients, sometimes requiring that a pacing lead be placed in thepatient prior to use. Further, interacting with the thrombotic materialoutside of the catheter may allow loose material to escape the capturemechanism.

SUMMARY OF THE INVENTION

In one embodiment of the present invention, a system for aspiratingthrombus includes an aspiration catheter having a supply lumen and anaspiration lumen, the supply lumen having a wall and a closed distalend, the aspiration lumen configured to couple to a vacuum source andhaving an interior wall surface, and an open distal end, an orifice inthe wall of the supply lumen, in fluid communication with the interiorof the aspiration lumen, the orifice located proximally of the opendistal end of the aspiration lumen and adjacent the closed distal end ofthe supply lumen, wherein the orifice is configured to create a spraypattern when pressurized fluid is pumped through the supply lumen suchthat the spray pattern impinges on the interior wall surface of theaspiration lumen when a distal end of the aspiration catheter isimmersed within an aqueous environment, and a disposable tubing sethaving a first conduit configured to couple to the supply lumen of theaspiration catheter to a fluid source, and a pump component associatedwith the first conduit and configured to detachably couple to a driveunit, such that motion from the drive unit is transferred to the pumpcomponent such that resultant motion of the pump component causes fluidfrom the fluid source to be injected through the supply lumen of theaspiration catheter, and through the orifice into the aspiration lumen.

In another embodiment of the present invention, a system for aspiratingthrombus includes an aspiration catheter having a supply lumen and anaspiration lumen, the supply lumen having a distal end, the aspirationlumen configured to couple to a vacuum source and having an interiorwall surface, and an open distal end, an orifice at or near the distalend of the supply lumen, in fluid communication with the interior of theaspiration lumen, the orifice located proximally of the open distal endof the aspiration lumen, wherein the orifice is configured to create aspray pattern when pressurized fluid is pumped through the supply lumensuch that the spray pattern impinges on the interior wall surface of theaspiration lumen when a distal end of the aspiration catheter isimmersed within an aqueous environment, and a disposable tubing sethaving a first conduit configured to couple the supply lumen of theaspiration catheter to a fluid source, and a pump component associatedwith the first conduit and configured to detachably couple to a driveunit, such that motion from the drive unit is transferred to the pumpcomponent such that resultant motion of the pump component causes fluidfrom the fluid source to be injected through the supply lumen of theaspiration catheter, and through the orifice into the aspiration lumen.

In another embodiment of the present invention, a method for delivery ofa drug includes providing a catheter including a supply lumen and anaspiration lumen, the supply lumen having a distal end, the aspirationlumen configured to couple to a vacuum source and having an interiorwall surface, and an open distal end, an orifice at or near the distalend of the supply lumen, in fluid communication with the interior of theaspiration lumen, the orifice located proximally of the open distal endof the aspiration lumen, wherein the orifice is configured to create aspray pattern when pressurized fluid is pumped through the supply lumensuch that the spray pattern impinges on the interior wall surface of theaspiration lumen when a distal end of the aspiration catheter isimmersed within an aqueous environment, providing a disposable tubingset having a first conduit configured to couple the supply lumen of thecatheter to a fluid source, and a pump component associated with thefirst conduit and configured to detachably couple to a drive unit, suchthat motion from the drive unit is transferred to the pump componentsuch that resultant motion of the pump component causes fluid from thefluid source to be injected through the supply lumen of the catheter,and through the orifice into the aspiration lumen, coupling the supplylumen of the catheter to a fluid source, wherein the fluid sourcecontains at least a first drug for intravascular delivery, inserting thecatheter within a blood vessel of a patient and advancing the catheterto a target site, coupling the pump component to a drive unit, andoperating the drive unit to cause the pump component to inject at leastsome of the first drug in the region of the target site.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of a system for aspirating thrombusaccording to an embodiment of the present invention.

FIG. 2 is a diagrammatic view showing more detail of the proximalportion of the system for aspirating thrombus of FIG. 1.

FIG. 3 is a diagrammatic view of the distal end portion of the systemfor aspirating thrombus of FIG. 1.

FIG. 4 is a plan view of disposable components of a system foraspirating thrombus according to an embodiment of the present invention.

FIG. 5 is a detailed view of detail 5 of FIG. 4.

FIG. 6 is a detailed view of detail 6 of FIG. 4.

FIG. 7 is a detailed view of detail 7 of FIG. 4.

FIG. 8 is a detailed view of detail 8 of FIG. 4.

FIG. 9 is a plan view of a distal end of an aspiration catheter of thesystem for aspirating thrombus of FIG. 4.

FIG. 10 is a sectional view of FIG. 9 taken through line 10-10, asviewed within a blood vessel.

FIG. 11 is a detailed view of detail 11 of FIG. 10.

FIG. 12 is elevation perspective view of a pump base according to anembodiment of the present invention.

FIG. 13 illustrates a piston of the system for aspirating thrombus beingcoupled to a saddle of a piston pump.

FIG. 14 is a cross-sectional view of the distal tip of the aspirationcatheter of FIG. 9.

FIG. 15 is a view a cassette for coupling to a pump base.

FIG. 16 is a sectional view of the cassette of FIG. 15.

FIG. 17 is a partially exploded view of the pump base of FIG. 12.

FIG. 18 is a graph of a pressure vs. time relationship of a piston pump.

FIG. 19 is an elevation view of a piston and a cassette of a piston pumpaccording to an embodiment of the present invention.

FIG. 20 is a graph of a pressure vs. time relationship of a piston pump.

FIG. 21 is a plan view of disposable components of a system foraspirating thrombus according to an embodiment of the present invention.

FIG. 22 is a detailed view of a catheter of the system for aspiratingthrombus of FIG. 21.

FIG. 23 is a detailed view of a tubing set of the system for aspiratingthrombus of FIG. 21.

FIG. 24 is an exploded view of a saline pump drive unit according to anembodiment of the present invention.

FIG. 25 is an exploded view of a disposable piston pump head of thesaline pump unit of FIG. 24.

FIG. 26 is a sectional view of an aspiration catheter of a system foraspirating thrombus within a blood vessel according to an embodiment ofthe present invention.

FIG. 27 is a sectional view of a catheter within a blood vesseldelivering a drug to a target site.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

For the following defined terms, these definitions shall be applied,unless a different definition is given in the claims or elsewhere inthis specification.

All numeric values are herein assumed to be modified by the term“about,” whether or not explicitly indicated. The term “about” generallyrefers to a range of numbers that one of skill in the art would considerequivalent to the recited value (i.e., having the same function orresult). In many instances, the terms “about” may include numbers thatare rounded to the nearest significant figure.

The recitation of numerical ranges by endpoints includes all numberswithin that range (e.g. 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and5).

As used in this specification and the appended claims, the singularforms “a”, “an”, and “the” include plural referents unless the contentclearly dictates otherwise. As used in this specification and theappended claims, the term “or” is generally employed in its senseincluding “and/or” unless the content clearly dictates otherwise.

The following detailed description should be read with reference to thedrawings in which similar elements in different drawings are numberedthe same. The drawings, which are not necessarily to scale, depictillustrative embodiments and are not intended to limit the scope of theinvention.

FIG. 1 is a diagrammatic figure depicting an assisted aspiration system10. The aspiration system 10 includes a remote hand piece 12 thatcontains a fluid pump 26 and an operator control interface 6. In onecontemplated embodiment, the system 10 is a single use disposable unit.The aspiration system 10 may also include extension tubing 14, whichcontains a fluid irrigation lumen 2 (or high pressure injection lumen)and an aspiration lumen 4, and which allows independent manipulation ofa catheter 16 without requiring repositioning of the hand piece 12during a procedure performed with the aspiration system 10. Extensiontubing 14 may also act as a pressure accumulator. High pressure fluidflow from the pump 26, which may comprise a displacement pump, pulseswith each stroke of the pump 26, creating a sinusoidal pressure map withdistinct variations between the peaks and valleys of each sine wave.Extension tubing 14 may be matched to the pump 26 to expand and contractin unison with each pump pulse to reduce the variation in pressurecaused by the pump pulses to produce a smooth or smoother fluid flow attip of catheter 16. Any tubing having suitable compliancecharacteristics may be used. The extension tubing 14 may be permanentlyattached to the pump 26 or it may be attached to the pump 26 by aconnector 44. The connector 44 is preferably configured to ensure thatthe extension tubing 14 cannot be attached to the pump 26 incorrectly.

An interface connector 18 joins the extension tubing 14 and the catheter16 together. In one contemplated embodiment, the interface connector 18may contain a filter assembly 8 between high pressure fluid injectionlumen 2 of the extension tubing 14 and a high pressure injection lumen36 of the catheter 16 (FIG. 3). The catheter 16 and the extension tubing14 may be permanently joined by the interface connector 18.Alternatively, the interface connector 18 may contain a standardizedconnection so that a selected catheter 16 may be attached to theextension tubing 14.

Attached to the hand piece 12 are a fluid source 20 and a vacuum source22. A standard hospital saline bag may be used as fluid source 20; suchbags are readily available to the physician and provide the necessaryvolume to perform the procedure. Vacuum bottles may provide the vacuumsource 22, or the vacuum source 22 may be provided by a syringe, avacuum pump or other suitable vacuum sources.

In one contemplated embodiment, the catheter 16 has a variable stiffnessranging from stiffer at the proximal end to more flexible at the distalend. The variation in the stiffness of the catheter 16 may be achievedwith a single tube with no radial bonds between two adjacent tubingpieces. For example, the shaft of the catheter 16 may be made from asingle length of metal tube that has a spiral cut down the length of thetube to provide shaft flexibility. Variable stiffness may be created byvarying the pitch of the spiral cut through different lengths of themetal tube. For example, the pitch of the spiral cut may be greater(where the turns of the spiral cut are closer together) at the distalend of the device to provide greater flexibility. Conversely, the pitchof the spiral cut at the proximal end may be lower (where the turns ofthe spiral cut are further apart) to provide increased stiffness. Insome embodiments, a single jacket may cover the length of the metal tubeto provide for a vacuum tight catheter shaft. Other features of catheter16 are described with reference to FIG. 3, below.

FIG. 2 is a diagrammatic view showing more detail of the hand piece 12and the proximal portion of assisted catheter aspiration system 10. Thehand piece 12 includes a control box 24 where the power and controlsystems are disposed. The pump 26 may in some embodiments be a motordriven displacement pump that has a constant output. The pumpdisplacement relationship to the catheter volume, along with thelocation of the orifice 42 (exit) of the catheter high pressure lumen 36within the aspiration lumen 38 (FIG. 3), ensures that no energy istransferred to the patient from the saline pump as substantially allpressurized fluid is evacuated by the aspiration lumen. A prime button28 is mechanically connected to a prime valve 30. When preparing thedevice for use, it is advantageous to evacuate all air from thepressurized fluid system to reduce the possibility of air embolization.By depressing the prime button 28, the user connects the fluid source 20to the vacuum source 22 via the pump 26. This forcefully pulls fluid(for example 0.9% NaCl solution, or “saline”, or “normal saline”, orheparinized saline) through the entire pump system, removing all air andpositively priming the system for safe operation. A pressure/vacuumvalve 32 is used to turn the vacuum on and off synchronously with thefluid pressure system. One contemplated valve 32 is a ported one wayvalve. Such a valve is advantageous with respect to manual or electronicvalve systems because it acts as a tamper proof safety feature bymechanically and automatically combining the operations of the twoprimary systems. By having pressure/vacuum valve 32, the possibility ofturning the vacuum on without also activating the fluid system iseliminated.

The operator control interface 6 is powered by a power system 48 (suchas a battery or an electrical line), and may comprise an electroniccontrol board 50, which may be operated by a user by use of one or moreswitches 52 and one or more indicator lamps 54. The control board 50also monitors and controls several device safety functions, whichinclude over pressure detection, air bubble detection, and vacuumcharge. A pressure sensor 64 monitors pressure (i.e. injectionpressure), and senses the presence of air bubbles. Alternatively, or inconjunction, an optical device 66 may be used to sense air bubbles. Inone contemplated embodiment, the pump pressure is proportional to theelectric current needed to produce that pressure. Consequently, if theelectric current required by pump 26 exceeds a preset limit, the controlboard 50 will disable the pump 26 by cutting power to it. Air bubbledetection may also be monitored by monitoring the electrical currentrequired to drive the pump 26 at any particular moment. In order for adisplacement pump 26 to reach high fluid pressures, there should belittle or no air (which is highly compressible) present in the pump 26or connecting system (including the catheter 16 and the extension tubing14). The fluid volume is small enough that any air in the system willresult in no pressure being generated at the pump head. The controlboard monitors the pump current for any abrupt downward change that mayindicate that air has entered the system. If the rate of drop is fasterthan a preset limit, the control board 50 will disable the pump 26 bycutting power to it until the problem is corrected. Likewise, a block inthe high pressure lumen 36 (FIG. 3), which may be due to the entry oforganized or fibrous thrombus, or a solid embolus, may be detected bymonitoring the electrical current running the pump 26. In normal use,the current fluxuations of the pump 26 are relatively high. For example,the pump 26 may be configured so that there is a variation of 200milliAmps or greater in the current during normal operation, so thatwhen current fluxuations drop below 200 milliAmps, air is identified,and the system shuts down. Alternatively, current fluxuations in therange of, for example, 50 milliAmps to 75 milliAmps may be used toidentify that air is in the system. Additionally, an increase in thecurrent or current fluxuations may indicate the presence of clot orthrombus within the high pressure lumen 36. For example, a current ofgreater than 600 milliAmps may indicate that thrombus it partially orcompletely blocking the high pressure lumen 36, or even the aspirationlumen 38 (FIG. 3).

A vacuum line 56, connected to the vacuum source 22, may be connected toa pressure sensor 58. If the vacuum of the vacuum source 22 is low (i.e.the absolute value pressure has decreased) or if a leak is detected inthe vacuum line 56, the control board 50 disables the pump 26 until theproblem is corrected. The pressure sensor 58 may also be part of asafety circuit 60 that will not allow the pump 26 to run if a vacuum isnot present. Thereby, a comprehensive safety system 62, including thesafety circuit 60, the pressure sensor 64 and/or the optical device 66,and the pressure sensor 58, requires both pump pressure and vacuumpressure for the system to run. If a problem exists (for example, ifthere is either a unacceptably low pump pressure or an absence ofsignificant vacuum), the control board 50 will not allow the user tooperate the aspiration system 10 until all problems are corrected. Thiswill keep air from being injected into a patient, and will assure thatthe aspiration system 10 is not operated at incorrect parameters.Alternatively, in lieu of a direct connection (e.g., electrical,optical), the pressure sensor 58 can be configured to send a wirelesssignal to the control board 50, or any other component (e.g., antenna)coupled to or in communication with the control board 50, to remotelycontrol operation of the pump 26. The remote control may be possible,whether the pump is within the sterile filed or outside the sterilefield.

FIG. 3 is a diagrammatic view of the distal end portion 68 of theassisted catheter aspiration system 10, showing more details of thecatheter 16. The catheter 16 in some embodiments is a single-operatorexchange catheter and includes a short guidewire lumen 34 attached tothe distal end of the device. The guidewire lumen 34 can be betweenabout 1 and about 30 cm in length, or between about 5 and about 25 cm inlength, or between about 5 and about 20 cm in length, or approximately13.5 cm in length. In other embodiments, a full-length guidewire lumen(extending the length of the catheter 16) may be used. For example, acatheter 16 sized to be used on peripheral blood vessels, includingperipheral arteries, may incorporate a full-length guidewire lumen. Insome embodiments, the aspiration itself may also serve as a guidewirelumen. An aspiration lumen 38 includes a distal opening 40 which allowsa vacuum (for example, from vacuum source 22) to draw thromboticmaterial into the aspiration lumen 38. A high pressure lumen 36 includesa distal orifice 42 that is set proximally of distal opening 40 by a setamount. For example, distal orifice 42 can be set proximally of distalopening 40 by about 0.508 mm (0.020 inches), or by 0.508 mm±0.076 mm(0.020 inches±0.003 inches) or by another desired amount. The orifice 42is configured to spray across the aspiration lumen to macerate and/ordilute the thrombotic material for transport to vacuum source 22, forexample, by lowering the effective viscosity of the thrombotic material.The axial placement of the fluid orifice 42 is such that the spraypattern interaction with the opposing lumen wall preferably produces aspray mist and not a swirl pattern that could force embolic material outfrom the distal opening 40. The spray pattern may be present at leastwhen a distal end of the catheter 16 is within an aqueous environment,such as a body lumen, including a blood vessel. The aqueous environmentmay be at body temperature, for example between about 35.0° C. and about40.0° C., or between about 36.0° C. and about 38.0° C. The system may beconfigured so that the irrigation fluid leaves the pump at a pressure ofbetween about 3.447 megapascal (500 pounds per square inch) and about10.342 megapascal (1500 pounds per square inch). In some embodiments,after a pressure head loss along the high pressure lumen 36, theirrigation fluid leaves orifice 42 at between about 4.137 megapascal(600 pounds per square inch) and about 8.274 megapascal (1200 pounds persquare inch), or between about 4.816 megapascal (650 pounds per squareinch) and about 5.861 megapascal (850 pounds per square inch).

FIG. 4 illustrates a system for aspirating thrombus 100 according to anembodiment of the present invention. The system for aspirating thrombus100 depicted in FIG. 4 represents disposable components 101, comprisinga tubing set 103 and an aspiration catheter 118, which are configured toattach to a vacuum source 22, a fluid source 20 (FIGS. 1 and 2), apressure monitor (not shown), and a pump base 200 (FIG. 12). The systemfor aspirating thrombus 100 is also configured to be used with aguidewire. Beginning with the components of the tubing set 103, a spike102 (shown in more detail in FIG. 5) is configured to couple to a fluidsource 20 such as a saline bag. The saline bag may have a volume ofsaline equal to about 1000 ml or about 500 ml. The saline may beheparinized, or may contain one or more therapeutic agents. The salinemay be at room temperature, or may be warmed or cooled. A connector 104(shown in more detail in FIG. 7), for example a luer connector, isconfigured to couple to a vacuum source 22. The vacuum source 22 may bea vacuum bottle having a volume of between 20 ml and 500 ml. The vacuumsource 22 may instead be a 60 ml syringe whose plunger is pulled backafter coupling to the connector 104. This may be a lockable plunger,which is locked in order to maintain the evacuated plunger position. Insome cases, the vacuum source 22 may be a 20 ml syringe or a 30 mlsyringe. An exemplary syringe with a lockable plunger is the VacLok®syringe sold by Merit Medical Systems, Inc. of South Jordan, Utah, USA.The vacuum source 22 may also be a vacuum pump, with or without acollection container. A pressure transducer 106 capable of measuringvacuum (including positive pressure sensors that are configured tomeasure positive pressure, but are capable of measuring negativepressure) is coupled to a vacuum line 108 via a y-connector 110. Signalsfrom the pressure transducer 106 travel along a cable 112 (FIG. 7),which also supplies voltage to the pressure transducer 106. A connector114 (also shown in FIG. 6) couples the cable 112 to a pressure monitoror to the pump base 200. A cassette 116 is a disposable componentattachable to the pump base 200 (FIG. 12) for allowing pressurizedinjection of a liquid injectate (such as saline). The cassette 116 isdescribed in more detail in relation to FIG. 6. The aspiration catheter118 having a distal end 120 is shown in more detail in FIG. 8.

Turning to FIG. 5, the spike 102 communicates with extension tubing 122.Liquid injectate is pumped downstream at the piston pump, which pullsmore liquid injectate (for example from a saline bag) through a checkvalve 126 and through a supply tube 130. An injection port 128 may beused for injecting other materials into the system, or for removing airor priming the system. The spike 102 may be packaged with a removableprotective spike cover 124.

The cassette 116, as seen in FIG. 6, pulls liquid injectate from thesupply tube 130, and pressurizes (in conjunction with the pump base 200)an injection tube 152. More detail of the cassette 116 will be describedalong with the description of the entire piston pump. FIG. 7 shows moredetail of the pressure transducer 106 for measuring the vacuum. Thepressure transducer 106 connects to the y-connector 110 with a luerfitting 154. The injection tube 152 and the vacuum line 108 communicateto lumens of a catheter shaft 142. For example, the injection tube 152may be fluidly connected to a distal supply tube 168 (FIGS. 9-11), forexample a polyimide or stainless steel or nitinol tube having highstrength thin walls. This distal supply tube 168 may reside within thecatheter shaft 142, with the annulus between forming an aspiration lumen160 (FIGS. 9-11). A strain relief 156 protects the catheter shaft 142from kinking and other damage. In any cases in which luer fittings 154are used (at any of the connections), a custom luer with an added o-ringmay be used in order to allow the connection to withstand elevatedpressures. In some embodiments, a bespoke connector may be utilized, toincrease high pressure endurance. In some embodiments, pressures as highas 6.89 megapascal (1,200 pounds per square inch) or greater may beachieved without leakage or without causing decoupling of the catheter.

Turning to FIG. 8, the aspiration catheter 118 is illustrated as asingle-operator exchange catheter and includes a guidewire tube 132attached to the distal end 120 on one side of the aspiration catheter118. The guidewire tube 132 can be between about 1 and about 30 cm inlength, or between about 5 and about 25 cm in length, or between about 5and about 20 cm in length, or approximately 13.5 cm in length. Theguidewire tube 132 has a distal end 136 and a proximal end 138, and asingle guidewire lumen 134 passing between the two ends 136, 138. Theguidewire lumen 134 may be configured to be compatible with a 0.014″guidewire, a 0.018″ guidewire, or a number of other guidewire diameters.A lumen inner diameter may be about 0.406 mm (0.016 inches) forcompatibility with a 0.014″ guidewire. The guidewire tube 132 may beconstructed of a number of materials, including nylon, polyethylene,PEBAX®, polyester, PET, or may be constructed from composite orcoextruded materials. For example an inner layer may comprise highdensity polyethylene or FEP, PTFE, ETFE, or other materials for highlubricity, and an outer layer may include PEBAX, nylon or othermaterials, for combination mechanical strength and flexibility. A tielayer may be used between the inner and outer layers, for example linearlow density polyethylene. The catheter 118 may include a compositecatheter shaft 142 having an inner support structure 144 covered with apolymer jacket 146. The inner support structure 144 may be a tubularbraid or one or more helical coils, for example, made with stainlesssteel flat or round wires. The inner support structure 144 may also bespiral cut hypodermic tubing, for example made from 304 stainless steelor nickel-titanium. The spiral cut hypodermic tubing may have a pitchmeasuring about 4 to 6 millimeters, or about 5 millimeters at theproximal end for increased stiffness, transitioning to a pitch of about0.75 to 1 mm or about 0.87 mm, at the distal end 150 of the innersupport structure 144. In between the these two different pitchsections, may be intermediate pitch sections, for example, a sectionhaving a pitch of between about 2 mm and about 5 mm, and another sectionhaving a pitch of about 1 mm to about 2.5 mm. The inner supportstructure 144 may end at a transition zone 148, so that the polymerjacket 146 alone extends to the distal end 136 of the aspirationcatheter 118. A catheter tip portion 140 is described in more detail inrelation to FIGS. 9-11.

FIGS. 9-11 show an open distal end 158 of an aspiration lumen 160 foraspirating thrombus. A skive 162 may be formed in the polymer jacket146, to aid entry of thrombus 164 that is aspirated into the aspirationlumen 160 (in the direction of arrow 180) by the combination of thevacuum created by the vacuum source 22. The skive 162 also minimizes thechances of the open distal end 158 being sucked against a blood vesselwall 166. A distal supply tube 168 has a closed distal end 170, forexample, it may occluded during manufacture using adhesive, epoxy, hotmelt adhesive or an interference member. Alternatively, the distalsupply tube 168 may be closed off by melting a portion of it. The distalsupply tube 168 has a lumen 176 extending its length and an orifice 172formed through its wall 174 at a location adjacent and proximal to theclosed distal end 170. The orifice 172 may have a diameter between about0.0508 mm (0.002 inches) and about 0.1016 mm (0.004 inches), or about0.0787 mm (0.0031 inches). The inner diameter of the distal supply tube168 may be between about 0.3048 mm (0.012 inches) and about 0.4826 mm(0.019 inches), or between about 0.3556 mm (0.014 inches and about0.4318 mm (0.017 inches) or about 0.3937 mm (0.0155 inches). The lumen176 of the distal supply tube 168 is a continuation of an overall flowpath emanating from the fluid source 20 including the extension tubing122, the supply tube 130, the interior of the cassette 116, and theinjection tube 152. In some embodiments, the lumen 176 of the distalsupply tube 168 may taper, for example, from an inner diameter of about0.3937 mm (0.0155 inches) at a proximal portion to an inner diameter ofabout 0.2974 mm (0.011 inches) at a distal portion. In some embodiments,the equivalent of a taper may be achieved by bonding different diametertubing to each other, resulting in a stepped-down tubing inner diameter.In some embodiments, different diameter tapered tubing may be bonded toeach other, for a combination of tapering and step-down of diameter. Asdescribed in conjunction with the piston pump, a pump output pressurewave of about 4.137 megapascal (600 pounds per square inch) to about5.516 megapascal (800 pounds per square inch) causes a liquid injectateto flow through the flow path, including a the distal supply tube 168(arrows 182), and causes a fluid jet 178 to exit the orifice 172 at ahigh velocity. The fluid jet 178, in absence of flow through theaspiration lumen 160 (for example if there is no vacuum), would impingeupon an inner wall 181 of the aspiration lumen 160 directly adjacent theorifice 172. Depending on the amount of vacuum present, the fluid jet,may curve as shown. The fluid jet 178 serves to macerate thrombus 164that enters the aspiration lumen 160, and dilutes it. The flow rate ofthe liquid injectate (e.g. saline) and the amount of vacuum arecontrolled so that about 50% to about 70% of the volume of the mixtureof the saline and blood flowing through the proximal aspiration lumen160 is blood. Or about 60% of the volume is blood. This maceration anddilution assures that there is continuous flow through the aspirationlumen 160 so that it will not clog. The fluid jet 178 is configured tobe contained within the aspiration lumen 160, and to not exit into ablood vessel or other body lumen.

The axial center of the orifice 172 is about 0.3302 mm (0.013 inches) toabout 0.4826 mm (0.019 inches) proximal to the most proximal portion ofthe open distal end 158, as illustrated by distance D in FIG. 11. FIG.14 is a cross-section of the catheter tip portion 140 at the axialcenter of the orifice 172. The orifice 172 it is oriented approximatelyalong a vertical midline 184 of the aspiration lumen 160, or within arange of ±a, there where angle a is about 20°. The angle a, may bevaried in different embodiments between about 1° and about 45°, orbetween about 20° and about 35°. The guidewire tube 132 may be securedto the polymer jacket 146 with attachment materials 186, such asadhesive, epoxy, hot melt or other materials. The guidewire tube 132 maybe secured along its entire length, or at discrete locations along itslength, in order to maximize flexibility. The distal supply tube 168 maybe secured within the aspiration lumen 160 with attachment materials188, such as adhesive, epoxy, hot melt or other materials. The polymerjacket 146 may comprise a number of different materials, includingPEBAX, nylon, or polyurethane. In some embodiments, the polymer jacketmay be partially melt bonded to the distal supply tube 162 and/or theguidewire tube 132, in order to minimize the wall thickness of theassembly.

FIG. 12 illustrates a pump base 200 for coupling the cassette 116 of thesystem for aspiration of thrombus 100. A housing 202 is attached to anIV pole clamp 204, and contains the control circuitry and the motor foroperating a piston pump system 300 (FIG. 13) which comprises thecombined pump base 200 and the cassette 116. By action of a motor andcam within the pump base 200, a saddle 206 is cyclically actuated (upand down) within a window 208 to move a piston 210 within the cassette116 (FIG. 13). Pegs 212 of the cassette 116 insert into cavities 216 inthe pump base 200. Biased snaps 214 lock into one or more grooves 218 inthe pump base 200. Either the cavities 216 or the grooves 218, may haveone or more switches which sense the presence of the cassette 116. Forexample, the cassette for one particular model may have a first number(or combination) of pegs 212 or biased snaps 214, which anotherparticular model may have a different number (or combination) of pegs212 or biased snaps 214, which is recognized by the system. A smoothsurface 224 of an elastomeric frame 222 engages edges 220 of thecassette 116, for enhanced protection. An upper space 226 is configuredto engage, or closely match the supply tube 130 and a lower space 228 isconfigured to engage, or closely match the injection tube 152. Thesaddle 206 has a semi-cylindrical cavity 236 which snaps over acylindrical engagement surface 238 on the piston 210. The saddle alsohas an upper edge 240 and a lower edge 242 for axially engaging a firstabutment 244 and a second abutment 246, respectively, of the piston 210.A user interface 230 on the pump base 200 has one or more buttons 232and one or more indicators 234, which allow the user to operate andassess the operation of the system 100. For example, the buttons mayinclude a start button to begin pumping, a stop button to stop pumping,a prime button to prime the system with a fluid injectate and purge outair, or a temporary pause button. Other data entry keys are alsopossible. The cassette 116 may include one or more interface components248. For example, a resistor, whose value the pump base 200 is able tomeasure via contacts 247, 249 when the cassette 116 is attached to thepump base. This allows the pump base to determine the appropriateparameter for operating a specific model of the system 100. For example,a first resistor having a first resistance may be used with a firstmodel and a second resistor having a second resistance may be used withanother model. Alternatively, the interface component 248 mayincorporate an RFID chip, such as a read RFID chip or a read/write RFIDchip. This may allow specific data (pump operating pressures, RPM ofmotor output, etc.) to be recorded within the pump base or to connectedhardware and identified for each patient.

FIGS. 15 and 16 illustrate the cassette 116 with most of its internalcomponents visible. FIG. 16 is a sectional view of the cassette 116. Thecassette 116 comprises an internal supply cylinder 252 and an internalinjection cylinder 254, which are cylindrical cavities extending withinthe cassette 116. The piston 210 includes a supply side shaft 256 and aninjection side shaft 258, the supply side shaft 256 including an o-ring266 for sealably interfacing with the supply cylinder 252 and theinjection side shaft 258 including an o-ring 268 for sealablyinterfacing with the injection cylinder 254. Each of the o-rings 266,268 are within a cylindrical groove 290, 292 around each respectiveshaft portion 256, 258. An internal ball valve 272 (FIG. 16) stopsinjectate (saline) from flowing through an internal channel 274 in thesupply side shaft 256 of the piston 210 when the piston 210 moves in afirst direction 276, but the internal ball valve 272 allows injectate toflow through the internal channel 274 and through an internal channel282 in the injection side shaft 258 when the piston 210 moves in asecond direction 278. The ball valve 272 is axially held between aspherical annular recess 284 in the interior of the supply side shaft256 and a recess having thru channels 286 in the injection side shaft258. The supply side shaft 256 and the injection side shaft 258 may beheld together with a threaded connection 288. When the piston 210 movesin the first direction 276, the injection side shaft 258 of the piston210 and o-ring 268 force injectate through the injection tube 152. Aprotective tube 280 is shown over the injection tube 152. In FIG. 15,the injection side shaft 258 is shown at the bottom of an injectionpulse. Injectate is filtered through an in-line filter 262, which may bea 40 to 50 micron filter, having an approximate thickness of 0.762 mm(0.030 inches). The in-line filter 262 is configured to keep particulateout of the injectate. Even though injectate is circulated through theaspiration catheter 118, and not into the blood vessel, the filteringprovided by the in-line filter 262 is an extra safety step. However,this step helps assure that particulate does not block the small orifice172 (FIG. 11). When the piston 210 moves in the second direction 278,the supply side shaft 256 of the piston 210 and the o-ring 266 sealablymove together within the supply cylinder 252, but the ball valve 272allows the injectate to pass through the internal channels 274, 282 ofthe piston 210 and fill the injection cylinder 254. The injectate isable to enter from the supply tube 130 through a check valve assembly270 comprising an o-ring 264 and a check valve 250. The check valve 250allows injectate to enter the interior of the cassette 116 from thesupply tube 130, but not to move from the cassette 116 to the supplytube 130. The check valve 250 may be configured so that air, due atleast in part to its low viscosity, will not be able to cause the checkvalve 250 to move (open), thus not allowing air to progress through thesystem. In some embodiments, the piston 210 may be a single piece(monolithic) design with a bore into which a check-valve is press-fit orbonded. A check valve compatible with this assembly may be supplied bythe Lee Company of Westbrook, Conn., USA.

The volume of injectate injected per cycle may range from about 0.02 mlto about 41 ml, or from about 0.04 ml to about 2.0 ml, or about 0.06 mlto about 0.08 ml, or about 0.07 ml. The usable volume (volume that canbe injected) of the injection cylinder 254 may be configured to be lessthan the usable volume (volume that can be filled from) of the supplycylinder 252, in order to assure sufficient filling of the injectioncylinder 254. For example, the usable volume of the injection cylinder254 may be about 0.05 ml to about 0.12 ml, and the usable volume of thesupply cylinder 252 may be about 0.07 ml to about 0.16 ml. A usablevolume ratio R_(U) of between about 1.15 and about 2.00, or betweenabout 1.25 and about 1.85, or about 1.40 is contemplated, where:

R _(U) =V _(SCU) /V _(ICU),

wherein:

-   -   V_(SCU)=Usable volume of the supply cylinder 252, and    -   V_(ICU)=Usable volume of the injection cylinder 254.

A mean flow rate of between about 5 ml/minute and about 100 ml/minute.In some embodiments for use in coronary applications, 20 ml/minute maybe desired. In some embodiments for use in peripheral applications, 50ml/minute may be desired.

FIG. 18 illustrates a graph 600 of a pressure (P) vs. time (T) curve 602of a piston pump. Peaks 604 and valley 606 of the curve 602 can bedependent upon the design of the piston and cylinders of the pistonpump, particularly of the usable volume ratio R_(U). Turning to FIG. 19,a piston 608 is illustrated having a first diameter D₁ and a seconddiameter D₂ measured at the compressed o-rings 601, 603 (when placedwithin cylinders 605 and 607 of a cassette 609). The diameters of thecylinders 605, 607 are thus also defined as diameters D₁ and D₂. Whenthe diameters D₁, D₂, and the lengths of the cylinders 605, 607 areadjusted such that the usable volume ratio R_(U) is optimized aspreviously described, a curve 610 as illustrated in FIG. 20 may beproduced. The curve 610 has less-defined peaks 614 and valleys 616, andthus produces less variation of flow amplitude, and a more balancedinjection.

The partially exploded pump base 200 in FIG. 17 illustrates the internalmechanisms for linear (up and down) actuation of the saddle 206, whichis attached to a saddle stage 310. A motor 302 is controlled by acircuit board 304 and operated by the user interface 230 (FIG. 12),whose indicators 234 are lit by LEDs 306. The motor 302 turns a cam 316,in which includes a path 330. The saddle stage 310 has a pin 318extending from its back side. The pin 318 may be press fit, bonded orscrewed in place within the saddle stage 310. The saddle stage 310 issecured with screws to two slides 312, 314 through holes 326, 328, suchthat rotary motion of the cam 316 causes the pin 318 to track along thepath 330 of the cam 316, thus causing the saddle stage 310 attached tothe slides 312, 314 to slide upward and downward in cyclic motion. Theshape of the cam determines the amount of acceleration and decelerationin the motion. Upper posts 322 and lower posts 324 serve as guidesand/or stops of the saddle stage 310. The connector 114 of the pressuretransducer 106 for measuring vacuum may be plugged into socket 308 (alsoshown in FIG. 12), and pressure related signals may be processed by thecircuit board 304. The entire pump base 200 is reusable.

The inner contour diameter of the cam 316 may be sized and/or shaped tocontrol the stroke length of the piston 210 and the amount ofpulsatility (i.e., the difference between the high and low pressure). Insome cases, decreasing the stroke length decreases the amount ofpulsatiliy. In applications within the heart, such as coronary arteryapplications, lowering the amount of pulsatility can reduce theincidence of bradycardia. To compensate for a lower stroke length, andto maintain a sufficient total flow rate, the speed of the rotation ofthe cam (i.e. rotations per minute), can be increased, for example byincreasing motor output speed, either by gearing or by increased appliedvoltage.

Another embodiment of a system for aspirating thrombus 800 isillustrated in FIG. 21. The system for aspirating thrombus 800 includes,three major components: the pump base 200 of FIG. 12, an aspirationcatheter 818, and a tubing set 803. The aspiration catheter 818 and thetubing set 803 represent disposable components 801, and the pump base200 is a reusable component. It is not necessary to sterilize the pumpbase 200 as it is kept in a non-sterile field or area during use. Theaspiration catheter 818 and the tubing set 803 may each be suppliedsterile, after sterilization by ethylene oxide gas, electron beam,gamma, or other sterilization methods. The aspiration catheter 818 maybe packaged and supplied separately from the tubing set 803, or theaspiration catheter 818 and the tubing set 803 may be package togetherand supplied together. Alternatively, the aspiration catheter 818 andtubing set may be packaged separately, but supplied together (i.e.,bundled). As shown in FIGS. 21 and 22. The aspiration catheter 818 andtubing set 803 share many of the same features as the aspirationcatheter 118 and tubing set 103 of FIG. 4, but are configured to alloweasier separation from each other, and additional proceduraladaptability. The aspiration catheter 818 has a distal end 820comprising a guidewire tube 832 having a distal tip 836, and a proximalend 819 comprising a y-connector 810. The catheter shaft 842 of theaspiration catheter 818 is connected to the y-connector 810 via aprotective strain relief 856. In other embodiments, the catheter shaft842 may be attached to the y-connector 810 with a luer fitting. They-connector 810 may comprise a first female luer 851 which communicateswith a catheter supply lumen (as in the catheter 118 of FIGS. 4, 8-11),and a second female luer 855 which communicates with a catheteraspiration lumen (as in catheter 118 of FIGS. 4, 8-11).

Turning to FIG. 23, the tubing set 803 is shown in more detail. A spike802 for coupling to a fluid source 20 (FIG. 1) allows fluid to enterthrough extension tubing 822 and a check valve 826, and into supply tube830. An optional injection port 828 allows injection of materials orremoval of air, as described in relation to previous embodiments. Acassette 816 is used in conjunction with the pump base 200, and issimilar in structure and function to the cassette 116 in FIGS. 15-16.Fluid is pumped into injection tube 852 from cassette 816. A male luer854 is configured to attach to the female luer 851 of the y-connector810.

Returning to FIG. 21, accessories 857 are illustrated that are intendedfor applying a vacuum source 22, including a syringe 849 having aplunger 867, to the catheter 818. The syringe 849 is attached to syringeextension tubing 859 via the luer 865 of the syringe 849. A stopcock 847may be used to hold maintain the vacuum, or the plunger 867 may be alocking variety of plunger. A luer 861 of the syringe extension tubing859 is connected to an pressure transducer 806, the pressure transducer806 having a male luer 863 for connection to a connector (e.g., femaleluer) 804 of vacuum line 808. A male luer 853 at the end of the vacuumline 808 may be detachably secured to the female luer 855 of they-connector 810 of the aspiration catheter 818. Signals from thepressure transducer 806 are carried through cable 812 to a connector814. The connector 814 is plugged into the socket 308 (FIG. 12) of thepump base 200. Pressure related signals may be processed by the circuitboard 304 of the pump base 200. The pressure transducer 806 may be powerfrom the pump base 200, via cable 812. The accessories 857 may also besupplied sterile to the user.

In use, the pump base 200 resides outside the sterile field. Becauseoperation of the pump base 200 may be controlled by the presence orabsence of a pressure, a user who is working in the sterile field mayturn the pump on or off without touching the non-sterile pump base 200.For example, the pump may be started by placing a vacuum on the system(e.g., pulling the plunger 867 of the syringe 849). The pump may in turnbe stopped by removing the vacuum on the system (unlocking the plunger867 of the syringe 849 and allowing to release, or opening the stopcock847). The syringe 849 or the combination syringe 849 and stopcock 847may act as a sterile on/off button of the pump vase 200. Alternatively,the aspiration catheter 818 may be initially used without the pump base200, with only aspiration being applied to the aspiration lumen. If incertain cases, if the aspiration lumen becomes clogged, the distal end820 of the aspiration catheter 818 may be backed off of the thrombus,and the pump base 200 and tubing set 803 may be coupled to theaspiration catheter 818, to then operate with forced saline injection,for increased aspiration, and clear the aspiration lumen. This will alsohelp stop any thrombus that is blocking the aspiration lumen from beinginadvertently delivered into the blood vessel of the patient.

FIGS. 24 and 25 illustrate a saline pump drive unit 400 having acompletely disposable pump head 500. The saline pump drive unit 400 isconfigured to be usable with the catheters 16, 118 described herein, orother embodiments of aspiration systems comprising fluid injection. InFIG. 24, a bottom case 402 and a top case 404 having a label 406 aresecured together with screws 408. Contained within the bottom case 402and top case 404 are a battery pack 410 and an electronic control module412. A battery cover 416 holds the battery pack 410 in place. In someembodiments, the battery pack 410 may supply a voltage of 18 Volts DC,but systems utilizing other voltages are possible. A user interface 414enables operation of the saline pump drive unit. A vacuum bottle sleeve418 may be used when a vacuum bottle is incorporated as the vacuumsource 22. A spike 420 is connectable to a fluid source 20, and fluidinjectate passes from the fluid source 20 through extension tubing 422to a disposable piston pump head 500. Saline may be primed through thesystem by an automatic priming (“self-priming”) system described hereinin relation to prior embodiments, or may be primed by gravity from asaline bag that is located (for example on an IV pole) above the rest ofthe system. A valve on the lowest portion of the system may be opened inorder to prime the entire system.

As illustrated in FIG. 25, the disposable piston pump head 500 isconfigured to couple to a motor shaft 504 of a motor 502, that ispowered by the battery pack 410 of the saline pump drive unit 400. Amotor plate 506 and a main body 508 of the disposable piston pump head500 are secured to each other with screws 510, and hold the internalcomponents of the disposable piston pump head 500. First and secondfollower plates 512, 514 are held together with screws 516 and bosses518 extending from the first follower plate 512. The first and secondfollower plates 512, 514 rotatably hold a cam 520. The cam may beassymetric (as illustrated) or alternatively may be symmetric. Theasymmetry may be incorporated in order to control the amount of noise inthe pump, the contours serving to customize the shape of the pressurewave, and of the function of the pump. First and second bushings 522,524 are rotatably held on first and second pins 526, 528. The pins 526,528 insert into cylindrical cavities 530, 532 in each of the followerplates 512, 514.

In use, a user attaches the disposable piston pump head 500 to the motor502 of the saline pump drive unit 400 by bringing the motor plate 506close to the motor shaft 504 so that a d-shaped hole 534 in the cam 520can be pressed over the d-shaped motor shaft 504. Alternatively, thed-shapes may be other non-circular shapes, including, but not limited toelliptical, oval, or rectangular. In operation the motor 502 turns themotor shaft 504, which in turn turns the cam 520. The cam 520 turns,forcing the bushings 522, 524 to push the first and second followerplates 512, 514 back and forth in a first direction 536 and a seconddirection 538. A saddle 544 is carried on the second follower plate 514,and a piston 210 may be coupled to the saddle 544 in the same manner asdescribed herein with other embodiments. A supply cylinder 552 and aninjection cylinder 554 in the main body 508 are analogous to the supplycylinder 252 and injection cylinder 254 of the cassette 116 of thesystem 100. The piston 210 of the cassette 116 may be used in thedisposable piston pump head 500. The labelled components related to thepiston 210 in FIG. 25 are similar to those described in relation to thepiston 210 in FIGS. 15 and 16. The outer diameter of the cam 520 may besized and/or shaped to control the stroke length of the piston 210 andthe amount of pulsatility (i.e., the difference between the high and lowpressure). In some cases, decreasing the stroke length decreases theamount of pulsatiliy. In applications within the heart, such as coronaryartery applications, lowering the amount of pulsatility can reduce theincidence of bradycardia. To compensate for a lower stroke length, andto maintain a sufficient total flow rate, the speed of the rotation ofthe cam (i.e. rotations per minute), can be increased, for example byincreasing motor output speed, either by gearing or by increased appliedvoltage. A vacuum spike 546 is used for coupling to the vacuum source22, for example a vacuum bottle held within the vacuum bottle sleeve418. A vacuum switch valve 540, which is activated against the bias of aspring 542, may be used to allow pump activation. For example, theelectronic control module 412 may be configured to initiate theoperation of the motor 502 automatically when the vacuum switch valve540 sends a signal corresponding to movement of the vacuum switch valve540, which occurs when a significant vacuum is achieved. This controlmay be instead of or in addition to control from a vacuum pressuretransducer, such as pressure transducer 106. The turning on of thevacuum may thus be used to simultaneously turn on the motor 502, so thata single input begins the operation of the saline pump drive unit 400.Additionally, a vacuum source 22 may be controlled by the electroniccontrol module 412 (for example, by opening or closing a solenoid), whena minimum injectate pressure is measured by an additional pressuretransducer. For example, when a pressure of about 0.62 megapascal (90pounds per square inch) or greater is measured, the vacuum may beactivated or communicated to the system. An advantage of the saline pumpdrive unit 400 is that the user is required only to assemble a singlecomponent onto the shaft 504 of the motor 502.

As previously described, the systems according to any of the embodimentsof the present invention may be configured such that active flow ofsaline (or other) injectate is not possible without concurrent vacuumbeing applied for aspiration. Also, the systems may be configured suchaspiration is not possible without saline (or other) injectate flow. Thesystems according to any of the embodiments of the present invention maybe configured such that current driving the pump (for example thecurrent driving the motor 302, 502) is monitored, or by any alternativemonitoring method, such that when a change in condition occurs, forexample, air in the injection system, or clogs in any of the catheterlumens or extension tubes, or leaks within the system, the system shutsdown, in order to avoid events such as injection of air into the bloodvessels, or catheter or system failure.

FIG. 26 illustrates an aspiration catheter 700 inserted within a bloodvessel 165. The aspiration catheter 700 includes a guidewire lumen 702secured to the distal end 704 of the aspiration catheter 700 whichallows the aspiration catheter 700 to be tracked over a guidewire 706. Asupply lumen 708 is secured within an aspiration lumen 710. The supplylumen 708 extends through a tapering tube 712. In some embodiments, thetapering tube 712 may be constructed of polyimide. In some embodiments,the tapering tube 712 may have a luminal inner diameter that tapers fromits proximal end to its distal end. For example, in some embodiments,the luminal inner diameter may taper from about 0.3937 mm (0.0155inches) to about 0.2794 mm (0.011 inches). The supply lumen 708 extendsgenerally parallel to the aspiration lumen 710, however a distal end 714of the tapering tube 712 curves towards an interior wall surface 716 ofthe aspiration lumen 710, thus allowing an open end 718 of the supplylumen 708 to act as an orifice for applying a spray pattern 720. Theopen end 718 of the supply lumen 708 may further promote a jet or sprayeffect by having an internal diameter that is less than about 0.203 mm(0.008 inches). In some embodiments, the open end 718 of the supplylumen 708 may have an internal diameter that is between about 0.076 mm(0.003 inches) and about 0.102 mm (0.004 inches). The center of the openend 718 orifice may in some embodiments be about 0.3302 mm (0.013inches) to about 0.4826 mm (0.019 inches) proximal to the most proximalportion 724 of the open distal end 722 of the aspiration lumen 710, asillustrated by distance D in FIG. 26. The most distal portion 726 of theopen distal end 722 of the aspiration lumen 710 is slightly distal ofthe most proximal portion 724 in the embodiment illustrated, and thushas an angled skive, but the skive angle A_(s) is not severe. A skiveangle A_(s) of between about 75° and about 89°, or between about 80° andabout 85° may be used, in order to allow a large portion of thrombusbeing pulled into the open distal end 722 of the aspiration lumen 710 tobe struck by high velocity exiting jet (e.g. saline) flow, asillustrated with the spray pattern 720.

FIG. 27 illustrates the catheter 700 of FIG. 26 being utilized todeliver a drug 730 to a target site 732 within a blood vessel 165. Thetarget site 732 may include an atherosclerotic lesion 728 and/or athrombus 734. Whereas the aspiration of thrombus, as in FIG. 26,involves actively applying a vacuum (e.g., from a vacuum source) on theaspiration lumen 710, the drug delivery illustrated in FIG. 27, thoughutilizing the same catheter 700, allows the metering of a fine,precision volume flow rate of drug 730 to be delivered into the vessel.This is achieved by having significantly less vacuum applied to theaspiration lumen 710, or no vacuum applied to the aspiration lumen. Theprecision metering in small, controlled volumes, provides efficient useof typically expensive drugs, with minimal wasted drug. In someembodiments, the drug 730 may be delivered at body temperature. In otherembodiments, the drug 730 may be warmed, and delivered at an elevatedtemperature, for example, to increase the activity and effectiveness ofa drug. This may be done, for example, to get a more effective dose,with a smaller volume of drug. In other embodiments, the drug 730 may becooled and delivered at a reduced temperature (i.e., in relation to thebody temperature). The drug 730 may be cooled to control the activitylevel, or to delay the activity of the drug (e.g., so that it is activedownstream, at a location that is not reachable by the catheter 700). Insome cases, the drug 730 may be cooled in order to apply a conjunctivetherapeutic cooling effect on the tissue being treated. In some cases,the therapeutic cooling effect may be achieved from cooled saline orother aqueous non-drug media alone.

Some of the drugs 730 which may be delivered include thrombolytic agents(clot busting drugs), such as streptokinase, tissue plasminogenactivator (t-PA), recombinant or genetically-engineered tissueplasminogen activator, tenecteplase (TNK), urokinase, staphylokinase,and reteplase. Alternatively, stem cells or “cocktails” containing stemcells may be delivered. In some cases, glycoprotein inhibitos (GPI's)may be injected through the supply lumen 708 of the aspiration catheter700. Saline or other aqueous solutions may be delivered alone forselective dilution of blood at the target site 732. In someapplications, a solution may be used which is capable of exhibiting aphase change, for example, when its pressure or temperature is changed.In these applications, a liquid may be injected that becomes a gas whenexiting from a small orifice, for example at the open end 718 of thesupply lumen 708. Alternatively, a gas may be injected that becomes aliquid when being force through a small orifice, such as the open end718 of the supply lumen 708. In any of the applications in which drugs730 or other materials are injected intravascularly through the catheter700, the injection of the drugs 730 or other materials may occur before,during, after, or instead of an aspiration procedure. Returning to theaspiration catheter 818 of FIGS. 21-22, if, during an aspirationprocedure, it is desired to deliver drugs down the supply lumen and intothe vessel, the tubing set 803 may be removed from the aspirationcatheter 818 by disconnecting the male luer 854 of the tubing set 803from the female luer 851 of the aspiration catheter 818, and the drugmay be injected directly into the supply lumen at the female luer 851,for example, by a syringe or metering system, including asyringe/syringe pump combination. By also removing the vacuum sourcefrom the female luer 855 of the aspiration catheter 818, when aspirationlumen now serves as an overflow, so that the fluid being delivered intothe patient (e.g., intravascularly) is maintained at a controlled rate.The volume of the supply lumen is relatively very small, so only a smallvolume of drug is needed to fill the supply lumen, and thus reach thedistal top of the aspiration catheter 818. This, at the end of theprocedure, very little drug is wasted, or needs to be disposed, allowingfor a very cost-effective procedure.

In the embodiments described herein, a sterile fluid path is providedextending all the way from the fluid source 20 to the distal opening40/open distal end 158 of the catheter 16, 118. In both the embodimentsof the system 100 of FIGS. 4-17, the system 800 of FIGS. 21-23, and theembodiments of FIGS. 24-25, a disposable catheter and disposable pumpset are configured to be supplied sterile, and coupled to a non-sterile(reusable) pump base 200 or pump motor 502. These combinations allow forreusability of the more expensive components, and for reusability (andmaximized sterility) of the less expensive components, thus maximizingcost containment and patient safety at the same time.

In some cases, parts or all of the devices described herein may be dopedwith, made of, coated with, or otherwise include a radiopaque material.Radiopaque materials are understood to be materials capable of producinga relatively bright image on a fluoroscopy screen or another imagingtechnique during a medical procedure. Some examples of radiopaquematerials can include, but are not limited to, gold, platinum,palladium, tantalum, tungsten alloy, polymer material loaded with aradiopaque filler, and the like. One or more hydrophilic or hydrophobiclubricious coatings may be used in order to improve trackability of theaspiration catheter 118 through the blood vessels.

In some instances, a degree of MRI compatibility may be imparted intoparts of the devices described herein. For example, to enhancecompatibility with Magnetic Resonance Imaging (MRI) machines, it may bedesirable to make various portions of the devices described herein frommaterials that do not substantially distort MRI images or causesubstantial artifacts (gaps in the images). Some ferromagneticmaterials, for example, may not be suitable as they may create artifactsin an MRI image. In some cases, the devices described herein may includematerials that the MRI machine can image. Some materials that exhibitthese characteristics include, for example, tungsten,cobalt-chromium-molybdenum alloys (e.g., UNS: R30003 such as ELGILOY®,PHYNOX®, and the like), nickel-cobalt-chromium-molybdenum alloys (e.g.,UNS: R30035 such as MP35-N® and the like), nitinol, and the like, andothers.

In some instances, some of the devices described herein may include acoating such as a lubricious coating or a hydrophilic coating.Hydrophobic coatings such as fluoropolymers provide a dry lubricity.Lubricious coatings improve steerability and improve lesion crossingcapability. Suitable lubricious polymers are well known in the art andmay include silicone and the like, hydrophilic polymers such ashigh-density polyethylene (HDPE), polytetrafluoroethylene (PTFE),polyarylene oxides, polyvinylpyrrolidones, polyvinylalcohols, hydroxyalkyl cellulosics, algins, saccharides, caprolactones, and the like, andmixtures and combinations thereof. Hydrophilic polymers may be blendedamong themselves or with formulated amounts of water insoluble compounds(including some polymers) to yield coatings with suitable lubricity,bonding, and solubility.

In one embodiment of the present invention, a system for aspiratingthrombus includes an aspiration catheter having a high pressure supplylumen and an aspiration lumen, the supply lumen having a proximal endconfigured to attach to a piston pump and a closed distal end, theaspiration lumen having a proximal end configured to attach to a vacuumsource and an open distal end; a first orifice in a side wall of thesupply lumen which communicates directly with the interior of theaspiration lumen, the first orifice located proximal to the open distalend of the aspiration lumen and adjacent the closed distal end of thesupply lumen; the piston pump configured to generate a cyclic pressurecycle when attached to the supply lumen, wherein the first orificecreates a spray pattern at least in conjunction with a peak of thepiston pump pressure cycle such that the spray pattern impinges on aninterior wall of the aspiration lumen when a distal end of theaspiration catheter is immersed within an environment having atemperature of between about 36° C. and 38° C., such that the spray isat an angle of between about 20° in each direction of the verticalmidline of the aspiration lumen.

In another embodiment of the present invention, a system for aspiratingthrombus includes an aspiration catheter having a high pressure supplylumen and an aspiration lumen, the supply lumen having a proximal endconfigured to attach to a piston pump and a closed distal end, theaspiration lumen having a proximal end configured to attach to a vacuumsource and an open distal end; a first orifice in a side wall of thesupply lumen which communicates directly with the interior of theaspiration lumen, the first orifice located proximal to the open distalend of the aspiration lumen and adjacent the closed distal end of thesupply lumen; the piston pump configured to generate a cyclic pressurecycle when attached to the supply lumen, wherein the first orificecreates a spray pattern at least in conjunction with a peak of thepiston pump pressure cycle such that the spray pattern impinges on aninterior wall of the aspiration lumen when a distal end of theaspiration catheter is immersed within an environment having atemperature of between about 36° C. and 38° C.; a disposable cassettehaving a supply cylinder, an injection cylinder and a piston, thedisposable cassette configured to releasably couple to at least a motorof the piston pump, the piston configured to actuate into the supplycylinder while actuating out of the injection cylinder, causing theinjection cylinder to increase its volume of a liquid injectate, thepiston further configured to actuate into the injection cylinder whileactuating out of the supply cylinder, causing the injection cylinder todecrease its volume by injecting the liquid injectate, and causing theliquid injectate to travel through the supply lumen of the aspirationcatheter.

In another embodiment of the present invention, a system for aspiratingthrombus includes an aspiration catheter having a high pressure supplylumen and an aspiration lumen, the supply lumen having a proximal endconfigured to attach to a piston pump and a closed distal end, theaspiration lumen having a proximal end configured to attach to a vacuumsource and an open distal end; a first orifice in a side wall of thesupply lumen which communicates directly with the interior of theaspiration lumen, the first orifice located proximal to the open distalend of the aspiration lumen and adjacent the closed distal end of thesupply lumen; the piston pump configured to generate a cyclic pressurecycle when attached to the supply lumen, wherein the first orificecreates a spray pattern at least in conjunction with a peak of thepiston pump pressure cycle such that the spray pattern impinges on aninterior wall of the aspiration lumen when a distal end of theaspiration catheter is immersed within an environment having atemperature of between about 36° C. and 38° C.; wherein the piston pumpincludes a supply cylinder, an injection cylinder and a piston, thepiston configured to actuate into the supply cylinder while actuatingout of the injection cylinder, causing the injection cylinder toincrease its volume of a liquid injectate, the piston further configuredto actuate into the injection cylinder while actuating out of the supplycylinder, causing the injection cylinder to decrease its volume byinjecting the liquid injectate, and causing the liquid injectate totravel through the supply lumen of the aspiration catheter; wherein thepiston is configured to engage with a saddle associated with the pistonpump, the saddle configured for cyclic linear motion, wherein motion ofthe saddle in a first direction actuates the piston out of the supplycylinder and motion of the saddle in a second direction actuates thepiston into the supply cylinder.

In another embodiment of the present invention, a system for aspiratingthrombus includes an aspiration catheter having a high pressure supplylumen and an aspiration lumen, the supply lumen having a proximal endconfigured to attach to a piston pump and a closed distal end, theaspiration lumen having a proximal end configured to attach to a vacuumsource and an open distal end; a first orifice in a side wall of thesupply lumen which communicates directly with the interior of theaspiration lumen, the first orifice located proximal to the open distalend of the aspiration lumen and adjacent the closed distal end of thesupply lumen; the piston pump configured to generate a cyclic pressurecycle when attached to the supply lumen, wherein the first orificecreates a spray pattern at least in conjunction with a peak of thepiston pump pressure cycle such that the spray pattern includes a jet;wherein the piston pump includes a supply cylinder, an injectioncylinder and a piston, the piston configured to actuate into the supplycylinder while actuating out of the injection cylinder, causing theinjection cylinder to increase its volume of a liquid injectate, thepiston further configured to actuate into the injection cylinder whileactuating out of the supply cylinder, causing the injection cylinder todecrease its volume by injecting the liquid injectate, and causing theliquid injectate to travel through the supply lumen of the aspirationcatheter; wherein a usable volume ratio R_(U) between the supplycylinder and the invention cylinder is between about 1.15 and about2.00. Additionally, the usable volume ratio R_(U) may be between about1.25 and about 1.85. Additionally, the usable volume ratio R_(U) may beabout 1.40.

In another embodiment of the present invention a method for delivery ofa drug includes providing a catheter including a supply lumen and anaspiration lumen, the supply lumen having a distal end, the aspirationlumen configured to couple to a vacuum source and having an interiorwall surface, and an open distal end, an orifice at or near the distalend of the supply lumen, in fluid communication with the interior of theaspiration lumen, the orifice located proximally of the open distal endof the aspiration lumen, wherein the orifice is configured to create aspray pattern when pressurized fluid is pumped through the supply lumensuch that the spray pattern impinges on the interior wall surface of theaspiration lumen when a distal end of the aspiration catheter isimmersed within an aqueous environment, providing a disposable tubingset having a first conduit configured to couple the supply lumen of thecatheter to a fluid source, and a pump component associated with thefirst conduit and configured to detachably couple to a drive unit, suchthat motion from the drive unit is transferred to the pump componentsuch that resultant motion of the pump component causes fluid from thefluid source to be injected through the supply lumen of the catheter,and through the orifice into the aspiration lumen, coupling the supplylumen of the catheter to a fluid source, wherein the fluid sourcecontains at least a first drug for intravascular delivery, inserting thecatheter within a blood vessel of a patient and advancing the catheterto a target site, coupling the pump component to a drive unit, andoperating the drive unit to cause the pump component to inject at leastsome of the first drug in the region of the target site.

It should be understood that this disclosure is, in many respects, onlyillustrative. Changes may be made in details, particularly in matters ofshape, size, and arrangement of steps without exceeding the scope of theinvention. The scope of the invention is, of course, defined in thelanguage in which the appended claims are expressed.

While embodiments of the present invention have been shown anddescribed, various modifications may be made without departing from thescope of the present invention. The invention, therefore, should not belimited, except to the following claims, and their equivalents.Embodiments of the present invention are contemplated to have utility ina variety of blood vessels, including but not limited to coronaryarteries, carotid arteries, intracranial/cerebral arteries, inferior andsuperior vena cavae and other veins (for example, in cases of deepvenous thrombosis), peripheral arteries, shunts, grafts, vasculardefects, and chambers of the heart. This includes, but is not limitedto, any vessel having a diameter of bout two mm or greater. Anaspiration catheter 118 outer diameter of about seven French or less iscontemplated for many of the applications, though in certainapplications, it may be larger. In some embodiments, an aspirationcatheter 118 diameter of about six French or less is contemplated.Embodiments of the present invention may even be used in non-vascularapplications, for example body lumens or cavities having materialaccumulations that need to be macerated and/or removed.

It is contemplated that various combinations or subcombinations of thespecific features and aspects of the embodiments disclosed above may bemade and still fall within one or more of the inventions. Further, thedisclosure herein of any particular feature, aspect, method, property,characteristic, quality, attribute, element, or the like in connectionwith an embodiment can be used in all other embodiments set forthherein. Accordingly, it should be understood that various features andaspects of the disclosed embodiments can be combined with or substitutedfor one another in order to form varying modes of the disclosedinventions. Thus, it is intended that the scope of the presentinventions herein disclosed should not be limited by the particulardisclosed embodiments described above. Moreover, while the invention issusceptible to various modifications, and alternative forms, specificexamples thereof have been shown in the drawings and are hereindescribed in detail. It should be understood, however, that theinvention is not to be limited to the particular forms or methodsdisclosed, but to the contrary, the invention is to cover allmodifications, equivalents, and alternatives falling within the spiritand scope of the various embodiments described and the appended claims.Any methods disclosed herein need not be performed in the order recited.The methods disclosed herein include certain actions taken by apractitioner; however, they can also include any third-party instructionof those actions, either expressly or by implication.

What is claimed is:
 1. A system for aspirating thrombus comprising: an aspiration catheter having a supply lumen and an aspiration lumen, the supply lumen having a distal end, the aspiration lumen configured to couple to a vacuum source and having an interior wall surface, and an open distal end; an orifice at or near the distal end of the supply lumen, in fluid communication with the interior of the aspiration lumen, the orifice located proximally of the open distal end of the aspiration lumen, wherein the orifice is configured to create a spray pattern when pressurized fluid is pumped through the supply lumen such that the spray pattern impinges on the interior wall surface of the aspiration lumen; a tubing set having a first conduit configured to couple the supply lumen of the aspiration catheter to a fluid source; a pump base comprising a pump and circuitry, the pump controlled by the circuitry, the pump configured to pump fluid from the fluid source through the supply lumen; and an extension tube having a second conduit having a sterile control and configured to be attached between the aspiration lumen and the vacuum source, the sterile control configured to be switched by a user between an open position and a closed position, wherein the open position couples the aspiration lumen to the vacuum source and causes the circuitry to start the pump. 